魏巍, 赵晓亮, 延军苏, 尤健, 张真发, 王勐, 宫立群, 张振, 张彬, 王长利. WNT5A 与小细胞肺癌临床特征的相关性研究及其对 细胞迁移作用的影响[J]. 中国肿瘤临床, 2017, 44(1): 46-51. DOI: 10.3969/j.issn.1000-8179.2017.01.275
引用本文: 魏巍, 赵晓亮, 延军苏, 尤健, 张真发, 王勐, 宫立群, 张振, 张彬, 王长利. WNT5A 与小细胞肺癌临床特征的相关性研究及其对 细胞迁移作用的影响[J]. 中国肿瘤临床, 2017, 44(1): 46-51. DOI: 10.3969/j.issn.1000-8179.2017.01.275
WEI Wei, ZHAO Xiaoliang, SU Yanjun, YOU Jian, ZHANG Zhenfa, WANG Meng, GONG Liqun, ZHANG Zhen, ZHANG Bin, WANG Changli. High expression of WNT5A in small cell lung cancer and promotion of cell migration by phosphorylation of JNK[J]. CHINESE JOURNAL OF CLINICAL ONCOLOGY, 2017, 44(1): 46-51. DOI: 10.3969/j.issn.1000-8179.2017.01.275
Citation: WEI Wei, ZHAO Xiaoliang, SU Yanjun, YOU Jian, ZHANG Zhenfa, WANG Meng, GONG Liqun, ZHANG Zhen, ZHANG Bin, WANG Changli. High expression of WNT5A in small cell lung cancer and promotion of cell migration by phosphorylation of JNK[J]. CHINESE JOURNAL OF CLINICAL ONCOLOGY, 2017, 44(1): 46-51. DOI: 10.3969/j.issn.1000-8179.2017.01.275

WNT5A 与小细胞肺癌临床特征的相关性研究及其对 细胞迁移作用的影响

High expression of WNT5A in small cell lung cancer and promotion of cell migration by phosphorylation of JNK

  • 摘要:
      目的  检测 WNT5A 在小细胞肺癌(small cell lung cancer,SCLC) 中的表达及其促细胞迁移作用的机制。
      方法  采用免疫组化的方法检测 79 例 SCLC 和 25 例正常肺组织中 WNT5A 的表达量。通过细胞划痕和 Transwell 小室检测 WNT5A 及 JNK 对 SCLC 细胞系 DMS153 迁移能力的作用,应用 Western blot 检测干扰 WNT5A 后磷酸化 JNK 含量的变化。
      结果  WNT5A 在 SCLC 中表达高于正常肺组织,并且与肿瘤的临床分期、淋巴转移及远处转移相关,WNT5A 的表达与神经元特性烯醇化酶(NSE) 、胃泌素释放肽前体(Pro-GRP) 也有明显相关性。干扰 WNT5A 导致 DMS153 迁移能力下降,应用 JNK 抑制剂 SP600125 能够阻止 WNT5A 造成的细胞迁移增加。
      结论  WNT5A 在 SCLC 中高表达,并且与肿瘤的转移相关,WNT5A 通过磷酸化 JNK 促进 SCLC 细胞迁移,并且可以作为 SCLC 的预测指标和治疗靶点。

     

    Abstract:
      Objective   The expression of WNT5A is associated with aggressive tumor biology and poor clinical outcomes of various types of cancer. However, its function in the cell migration of small cell lung cancer (SCLC) should be elucidated.
      Methods   The expres-sion of WNT5A in SCLC and normal lung tissues was detected by immunohistochemisty. The correlation between the expression and clinical characteristics of WNT5A was analyzed. The function of WNT5A in regulating cell migration was studied in DMS153 cell line in vitro. Small interfering RNA (SiRNA) was used to knock down WNT5A. Wound healing and Transwell tests were used to determine the migration rate of DMS153. The phosphorylated JNK expression was detected by Western blot analysis.
      Results   The WNT5A expression was higher in SCLC tissues than that of normal lung tissues. WNT5A was correlated with clinical stages, lymph nodes, and distance me-tastasis in SCLC. The high expression of WNT5A was accompanied by abnormal levels of NSE and Pro-GRP. The WNT5A phosphoryla-tion of JNK promoted cell migration in vitro.
      Conclusion   The expression of WNT5A in SCLC is high and correlated with tumor metasta-sis. The influence of WNT5A/JNK on the cell migration property of DMS153 supports the concept that WNT5A can initiate the cell mi-gration of SCLC, which suggested that WNT5A may be a marker and can be potentially used as an effective therapeutic target for the SCLC metastasis.

     

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